Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
复制标题
哺乳动物导管素抑制细菌生物膜形成和促进中性粒细胞多方面免疫功能的差异能力
DOI：
10.3390/ijms21051871
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发表时间：
2020
影响因子：
5.6
通讯作者：
Siguo Liu
中科院分区：
文献类型：
--
作者：
Fang Xie;Yanan Zan;Xinyuan Zhang;Huihui Zhang;Mingjie Jin;Wanjiang Zhang;Yueling Zhang;Siguo Liu
哺乳动物cathelicidins作为有效的杀微生物分子用于控制细菌感染，并且被认为是传统抗生素的有前途的替代品。它们调节宿主免疫应答的能力以及它们的杀菌活性对于治疗干预是必不可少的。在这项研究中，我们比较了抗菌肽BMAP-27、BMAP-34、mCRAMP和LL-37的杀菌活性、抗菌膜活性和免疫调节特性，并使用小鼠肺部感染模型评估了BMAP-27和LL-37组合的治疗效果。我们的研究结果表明，所有四种cathelicidins有效地杀死细菌通过快速诱导膜透化，和BMAP-27表现出最优秀的杀菌活性对不同的细菌病原体。BMAP-27、mCRAMP和LL-37有效抑制生物膜形成，而BMAP-34、mCRAMP和LL-37通过刺激中性粒细胞的趋化性、诱导活性氧的产生和促进中性粒细胞胞外陷阱的形成而发挥免疫调节功能，具有不同程度的功效。值得注意的是，BMAP-27和LL-37的组合有效地增强了铜绿假单胞菌的清除并减少了体内器官损伤。总之，这些发现强调了鉴定具有不同有益特性的哺乳动物cathelicidins的适当协同组合可能是对抗细菌感染的有效策略。
Mammalian cathelicidins act as the potent microbicidal molecules for controlling bacterial infection, and are considered promising alternatives to traditional antibiotics. Their ability to modulate host immune responses, as well as their bactericidal activities, is essential for therapeutic interventions. In this study, we compared the bactericidal activities, antibiofilm activities and immune-modulatory properties of cathelicidins BMAP-27, BMAP-34, mCRAMP, and LL-37, and evaluated the therapeutic efficacy of the combination of BMAP-27 and LL-37 using a mouse pulmonary infection model. Our results showed that all of the four cathelicidins effectively killed bacteria via rapid induction of membrane permeabilization, and BMAP-27 exhibited the most excellent bactericidal activity against diverse bacterial pathogens. BMAP-27, mCRAMP, and LL-37 effectively inhibited biofilm formation, while BMAP-34, mCRAMP and LL-37 exerted immunomodulatory functions with varying degrees of efficacy by stimulating the chemotaxis of neutrophils, inducing the production of reactive oxygen species, and facilitating the formation of neutrophil extracellular traps. Of note, the combination of BMAP-27 and LL-37 effectively enhanced the clearance of Pseudomonas aeruginosa and reduced the organ injury in vivo. Together, these findings highlight that identifying the appropriate synergistic combination of mammalian cathelicidins with different beneficial properties may be an effective strategy against bacterial infection.